Hypotheses and Current Treatment Options For Castration Resistance In Prostate Cancer

Abstract

Prostate cancer (PCa) is the most common male cancer and is known to affect around one in eight males in the United States. However, it tends to progress slowly and is even curable in the early stages of the disease. Androgen receptor (AR) hyperactivity and overexpression are present in almost all cases of PCa. Targeting AR with androgen receptor signaling inhibitors (ARSIs) has proven effective at slowing tumor progression by chemically castrating the patient. However, this is not a permanent solution, as all tumors treated with ARSIs eventually become castration-resistant PCa (CRPC). This could be due to a myriad of reasons, such as mutated variants of AR, selective pressure from the use of ARSI drugs eliminating cells that express higher AR (AR+), or the activation of alternative pathways.

Additionally, mutated variants of AR may bind to precursors or splice variants of androgens and be unaffected by ARSIs; the tumors themselves may produce more androgens, or the tumor cells may become androgen-independent through the alternate pathways. Further treatment is based on a case-to-case basis depending on various clinical or molecular features, such as the patient’s performance status, cancer grade or stage, and dynamic changes in prostate-specific antigen. Options include chemotherapy, intensified androgen deprivation therapy, and targeted therapy for specific molecules. Research for more effective approaches to treating CRPC is currently underway.